KO of <i>grp-1</i>, a GEF that stimulates Arf and PIP5K/PPK-1 to increase production of PIP2 substrate for the IIS cascade, provides neuroprotection.

<p>Left: a histogram showing a decrease in neurodegeneration upon KO of <i>grp-1</i> (a second independent cross gave very similar distribution, not shown) **: p<0.05; ***: p<0.01. Right: Nomarski/DIC images of neurodegeneration in head neurons. Anterior left, dorsal top, the nerve ring area is shown (located between the two bulbs of the pharynx), red arrows indicate degenerating neurons. A typical level of neurodegeneration in our excitotoxicity strain was depicted previously <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0113060#pone.0113060-Mano2" target="_blank">[43]</a>. We note that the extent of neurodegeneration varies among individual animals of the same genotype. Here, the upper image depicts an individual L3 animal from our excitotoxicity strain with an unusually high level of neurodegeneration. The extensive neurodegeneration seen in such untypical animals is evened out in the large number of animals used for each bar in our histograms (usually >90 animals in the most informative stages), bringing average neurodegeneration levels in our excitotoxicity strain (<i>glt-3;nuIs5</i>) to ∼4.5 dying head neurons/L3 animal. The bottom image depicts a typical <i>grp-1;glt-3;nuIs5</i> L3 animal, a strain that typically shows 2–3 dying head neurons/L3 animal.